Management of traumatic brain injury in an aging population: Role of S100, CT and anticoagulation in 10.051 patients

Management of traumatic brain injury in an aging population: Role of S100, CT and anticoagulation in 10.051 patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Management of traumatic brain injury in an aging population: Role of S100, CT and anticoagulation in 10.051 patients Clemens Clar, Paul Puchwein, Maximilian Moshammer, Patrick Sadoghi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6120248/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective The aim of this study was to investigate the benefit of the S100B level as a substitute for computed tomography (CT) in assessing brain injury in cases of traumatic brain injury (TBI). The hypothesis was that the S100B level would exhibit high negative sensitivity, thereby potentially obviating the need for CT scans and the associated radiation exposure in certain patients. Methods A cohort of 11,504 patient cases with TBI was collected from 04/2016 to 07/2022 at a level I trauma centre, where both CT scans and S100B measurements were performed. Those cases were classified and coded based on diagnosis, age and pathology. These results were analyzed with respect to radiologically diagnosed pathologies and the levels of S100B. Subsequently, a comparison was made to assess the correlation between pathology findings and negative S100B levels. Results Out of the 11,504 cases included in this study, 6% showed evidence of intracranial hemorrhage (ICH) and possible neurocranial fracture while 5% exhibited neurocranial fractures without concurrent ICH. The patient cohort of 3,920 individuals under known anticoagulation medication revealed that 5% displayed signs of ICH and possible neurocranial fracture and 4% exhibited neurocranial fractures without concurrent ICH. 483 cases with valid S100B measurements were identified of those, 36% were treated as inpatients showing an NPV of 73%, while 64% received outpatient care showing an NPV of 98%. Conclusions We found a clear and significant correlation between a negative S100B level and normal CT scan. We believe that the determination of S100B levels significantly reduces the radiation exposure for TBI patients. Traumatic brain injury S100B level Biomarkers Figures Figure 1 Figure 2 Figure 3 Introduction Traumatic brain injury (TBI) is a brain injury commonly caused by trauma, leading to a wide range of symptoms. In Austria the incidence of TBI is 303/100000 with a case fatality rate (CFR) of 3,6% and a mortality rate (MR) of 11/100000 which mirrors the numbers of other detected European countries 1 . Furthermore, worldwide over 10 million TBIs can be diagnosed annually 1 , 2 . There is a big gap between the age of patients and the incidence of TBI, heading from 149/100000 for the age of 40–44 to 1213/100000 for the age of 85–89 1 . People of advanced age usually suffer from comorbidities like dementia or coronary heart disease (CHD) and are therefore exposed to an increased risk of falling. In addition, the number of blood-thinned patients increases with age, which also increases the risk of TBI 2 . Diagnosis of TBI often involves interdisciplinary approach and brain imaging techniques such as CT scanning 3 . Because many emergency departments perform a CT-Scan as their standard diagnostic tool after head injuries, this leads to long waiting periods, a waste of resources and perhaps an unnecessary high exposure of patients to radiation. The decision to perform a CT scan is influenced by various factors, including the severity of symptoms, timing of the injury and the type of trauma. The indication for a brain CT scan is partially dependent on the patients clinical presentation, which can be misjudged due to comorbidities like dementia, for example. This is because the symptoms of TBI and this condition can be quite similar. In order to achieve sufficient differentiation between these pathologies, the establishment of clear guidelines and scoring systems is indispensable. Scores such as the Canadian CT Head Rule or the New Orleans Criteria have been distinguished by their high sensitivity 4 . Nevertheless, the potential influence of dementia on the results has not been accounted for. Furthermore, diagnostic tools that are not of a radiological nature can be utilized. As an alternative to the CT scan, which requires radiation, the S100B level has emerged as a promising biomarker-based approach in recent years for diagnosing TBI 3 , 5 . S100B is a low affinity calcium-binding protein expressed in glial and Schwann cells and is released during an astroglial injury 6 , 7 . Measuring S100B level in the blood can aid in diagnosing TBI and determining the severity of the injury. Some studies suggested that S100B level may serve as a decision-making tool for the necessity of CT scanning 8 . We already see a widespread use of that serum marker in certain clinical situations. Guidelines, such as those of the Scandinavian Neurotrauma Committee are already in use of that blood parameter 9 . A more standardized use of this value could prevent almost every third CT 10 – 13 . In the following study, we investigated the evidence between S100B level and the need for CT scans in patients with suspected TBI. The aim of this study was to detect whether measuring S100B level can be used as an additional diagnostic criterion for CT indication in TBI patients, and if this can help avoid unnecessary CT scans and lead to a reduction in radiation exposure and to a significant improvement of patient outcome. The hypothesis was that the S100B level would exhibit high negative sensitivity, thereby potentially obviating the need for CT scans and the associated radiation exposure in certain patients. Materials and Methods Study design: A retrospective single center study was conducted in order to investigate the association between the negative sensitivity of the S100B value and the radiological detection of TBIs. The investigation period ranged from 04/2016 to 07/2022. There was a total of 11504 cases collected. Participants: All patients admitted to the emergency department of a level I trauma center with a traumatic brain injury were included. The diagnosis of TBI was determined through the following possible pathways: A patient without acute life-threatening conditions underwent a blood sample collection after a clinical examination by a physician to measure the S100B value. If the S100B value was positive, an urgent CT scan was performed. However, if the S100B value was negative, a physical examination followed by an CT scan was conducted to exclude relevant pathological conditions. If the patient was on anticoagulation at the time of the accident, a CT scan was always performed immediately due to the increased risk of cerebral haemorrhage. Patients with instable vital parameters or altered neurological status were diagnosed using an urgent CT scan, followed by the measurement of the S100B value after the radiological examination. Those patients, which underwent a CT examination as the initial procedure analyzed. This data was then used to determine the frequency of ultimately unnecessary radiation dosage. Furthermore, within the cohort under investigation, the cases were documented to identify the number of patients requiring hospital admission. A patient was included in the 'Anticoagulation' subgroup if such medication had been recorded in the Hospital Information System (HIS) or if a specific anticoagulant could be determined through medical history taking. The following medications were included: Coumarins, Heparin and derivative substances, Synthetic pentasaccharide inhibitors of factor Xa, and direct oral anticoagulants (DOACs), direct factor Xa inhibitors and direct thrombin inhibitors. In this collective, the comorbidities of individual patients were assessed to see whether the condition of “Dementia” is associated with an increased risk of hospitalization. A patient was included in the “Dementia” subgroup if this condition had been recorded in the HIS in the past or had been diagnosed by a specialist. Since this study is randomized and does not allow any follow-up of patient data, a declaration of consent for participation was not necessary, ethical approval was obtained. Intervention: The S100B value was determined by taking bloodsample through an EDTA tube. This blood sample was then sent to the laboratory at the hospital and analyzed by machine. It is important to mention, that blood samples were only allowed for analysis when taken within the time frame of 30 minutes to 6 hours post-trauma. The threshold for a positive S100B value was set at 0.105 µg /L. Overall, this value was determined upon arrival in the emergency. Statistical analysis: The patient data was extracted from the HIS. All data were scanned by two independent individuals to minimize errors. These included structured data, like age, gender, coded diagnosis, etc., as well as the clinical reports of the CT scans. The radiological findings were prepared by experienced specialists in radiology and double-checked multiple times. Based on this data cohorts were formed according to age, gender, comorbidities, outpatient/inpatient treatment, diagnosis, and CT findings. For the CT findings, a coding system using 0, 1, and 2 was implemented, where 0 represented a CT scan without acute pathologies, 1 included all recent ICH with or without recent neurocranial fracture, and 2 denoted recent neurocranial fracture without ICH. Post hoc power analysis according to Hoenig and Heisey was calculated according to the magnitude of differences of our main endpoints and revealed that the included number of cases (11,504) was sufficient to reveal a power greater than 80% with a p-value less than 0,05. 14 If a CT finding exhibited motion artifacts that prevented sufficient interpretation or if the coding was erroneous, it did not meet the requirements for inclusion and was therefor excluded from this study. Results Out of the 11,504 cases included in this study, 3,157 (27%) were initially classified as inpatients and 8,338 (73%) as outpatients. Subsequently, their CTs were categorized as follows: Among the inpatients, 1,833 (58%) exhibited normal CT scans, 605 (19%) showed signs of ICH and/or recent skull fracture, and 301 (10%) displayed recent skull fractures without concurrent ICH (Fig. 1 ). Additionally, 418 (13%) cases did not meet the requirements and were excluded. Among the outpatients, 7,586 cases (91%) presented normal CT findings, 59 (1%) displayed signs of ICH and/or skull fracture, 265 (3%) showed recent skull fractures without signs of ICH, and 437 (5%) cases were excluded. Upon analyzing the entire patient cohort collectively, pathological findings were discovered in 1,230 (11%) out of 11,504 CT scans. Among these, 1230 (11%) CT scans 664 cases (6%) showed evidence of ICH and possible skull fracture and 566 (5%) exhibited skull fractures without concurrent ICH. A total of 9,419 (82%) CT scans were unremarkable, and 855 (7%) had to be excluded. Consequently, a gender-specific analysis was carried out. Among the inpatients, there was a ratio of 1,850 males (59%) to 1,307 females (41%), whereas among the outpatients, there were 4,533 females (54%) and 3,814 males (46%). In the age comparison between inpatient and outpatient treatment, a median age of 64 years was observed for inpatients compared to 74 years for outpatients, with mean ages of 60.7 and 65.6 years, respectively (Fig. 2 , 3 ). Subsequently, all patients were scanned for surgical interventions documented in the hospital IT system. Among the 8,338 patients treated on an outpatient basis, 28 individuals (0.03%) had recorded surgical procedures. Among the 3,157 inpatients 116 (4%) had documented surgical interventions. A subgroup analysis was performed on 1,445 patients with pre-existing dementia. While 1,180 (82%) exhibited normal CT scans, 111 (7%) pathological findings were identified with 63 cases (4%) showing signs of ICH with or without possible skull fracture and 48 (3%) exhibiting skull fractures without concurrent ICH. 154 (11%) CT scans were excluded from analysis. The patient cohort of 3,920 individuals under known anticoagulation medication revealed that 3,211 (82%) CT scans were unremarkable, 200 (5%) displayed signs of ICH and possible skull fracture, 153 (4%) exhibited skull fractures without concurrent ICH, and 356 (9%) scans were deemed inconclusive. Out of the total 11,504 cases available, 483 cases with valid S100B measurements were identified, comprising 232 (48%) males and 251 (52%) females. Among this subgroup, 172 (36%) were treated as inpatients, while 311 (64%) received outpatient care. In the age comparison between inpatient and outpatient treatment, a median age of 52 and 32 years, respectively, was determined, with mean ages of 52 and 39 years. The patient cohort undergoing outpatient treatment demonstrated, in 98% of cases with a normal S100B value, concurrent CT scans revealing no recent pathology, thereby indicating an 75% sensitivity of the S100B value. The inpatient cohort exhibited a sensitivity of 80%, and in 73% of cases with a normal S100B value, recent bleedings could not be detected in the CT scans. Discussion The aim of this study was to detect whether measuring S100B level can be used as an additional diagnostic criterion for CT indication in TBI patients, and if this can help avoid unnecessary CT scans and lead to a reduction in radiation exposure and to a significant improvement of patient outcome. The hypothesis was that the S100B level would exhibit high negative sensitivity, thereby potentially obviating the need for CT scans and the associated radiation exposure in certain patients. The following study revealed a clear and significant correlation between a negative S100B level and a normal CT scan, with the NPV being 98% for outpatients and 80% for inpatients. The initial treatment of TBIs is a highly discussed topic worldwide. In addition to the CT scan, the gold standard diagnostic tool, there has been a significant increase in the number of publications on non-ionizing diagnostic tools for TBI such as the biomarker S100B, which was investigated in this study. Scandinavia even reconsidered the international guidelines and decided to include the S100B value 15 . According to these guidelines, the determination of the S100B value is indicated if there is no other risk factor for cerebral pathology present besides unconsciousness and/or vomiting. Therefore, patients on anticoagulation and/or older than 65 years are excluded, which means that this patient group is more frequently exposed to radiation 16 . This study clearly confirmed this hypothesis, as risk patients such as patients on anticoagulation had a higher risk of unnecessary CT admission without recent pathology. Considering, that an exposure of radiation increases the lifetime risk of developing a malignancy by far, it is essential to evaluate every possibility to avoid unnecessary radiation 17 . To assess the increased risk of cancer, the dose used in CT and frequency of performed scans plays an essential role, as higher dosage and large numbers of CTs are associated with an elevated risk of cancer 18 , 19 . The average dose for an acute brain CT scan is approximately 1–3 mSv at the detected Level I Trauma center. The following study has demonstrated that around 82% of all CT examinations conducted for TBI did not reveal any pathological findings related to traumatic injuries. Consequently, these patients were exposed to unnecessary radiation. To minimize the risk of unnecessary radiation exposure in the future, the evaluation of new scores and guidelines for CT imaging is strongly indicated 20 , 21 . Beside radiation issues, economic aspects and 24h availability of CTs and evaluating radiologists could be limiting factors in overloaded health systems worldwide. Furthermore, we explored the comorbidity of "dementia" as a risk factor for hospital admission following TBI. As we demonstrated that only 7% of CT scans in this cohort revealed recent pathology, compared to 11% in the general cohort, the hypothesis that patients with dementia are at an increased risk of unnecessary radiation exposure after TBI was unequivocally confirmed. Clinical diagnosis may be complicated by the overlap of symptoms between dementia and TBI, potentially leading to a more frequent resort to diagnostic measures than necessary. Cognitive limitations typical for dementia and issues in verbal communication can exaggerate the perceived severity of the accident, providing a plausible explanation for the outcomes observed in the subsequent study 22 . Therefore, a new or adapted screening algorithm, including the development of certain scores and specific guidelines would be warranted to impede the overuse of CT scans in that patient group. It was also evident that the cohort of patients under anticoagulation treatment exhibited fewer percentage of detected pathologies overall compared to the entire patient collective. This suggests, among other factors, that the increased risk of bleeding due to anticoagulation lead to a more frequent reliance on CT scans as the primary diagnostic tool. In cases like these, in order to opt for a lower-radiation diagnostic approach, it is clearly indicated to either develop new scoring systems that prominently incorporate the aforementioned factors or to adapt existing ones, such as the "New Orleans criteria" or "Canadian CT head rule," to mitigate biases arising from the mentioned pathologies 4 , 23 . When comparing inpatient and outpatient populations, it becomes evident that both the median and average age of the inpatients were significantly higher, indicating an increased likelihood of hospitalization for older individuals after TBI. This result highlights a pronounced disparity in the treatment of traumatic brain injuries based on age, with older patients being subjected to more extended and intensive therapy. Given that more than half of the hospitalized patients exhibited no recent pathology in CT scans, this further underscores the importance of optimizing clear healthcare strategies and establishing well-defined standards. Considering that a CT scan costs an average of 250 Euros at the detected hospital, it becomes evident that from an economic perspective, every unnecessary CT scan should be avoided to prevent financial burden on the healthcare system. Additionally, performing a CT scan requires at least one radiologist and a radiological assistant, further adding to the financial implications. This aspect is further emphasized when examining the costs associated with hospitalization, where daily costs of approximately 1293 Euros are incurred per day at the hospital. Thus, implementing new scores and guidelines, as previously discussed, could also benefit the healthcare system by reducing financial burdens. Limitations: We opted to consider the S100B value as negative if it falls below < 0.105 µg/L, as this reference value is commonly cited in the literature 15 , 24 . However, the possibility of a number of subclinical, undetected brain injuries or long-term damages cannot be definitively excluded, as no follow-up was conducted. This study did not differentiate based on ethnic background, which, according to Abdesselam et al. 25 , is also an influential factor. Nonetheless, the majority of the patients included were Caucasian, reflecting the demographic composition of Austria. Conclusion The following study revealed a clear and significant correlation between a negative S100B level and normal CT scan. We believe that the determination of S100B levels can significantly reduce the radiation exposure for TBI patients. Clear communication of therapeutic aims (e.g. do not escalate, comfort terminal care) in patients with dementia could also help to avoid unnecessary imaging and admission of patients. Abbreviations CFR Case fatality rate CHD Coronary heart disease CT Computed tomography DOACs Direct oral anticoagulants HIS Hospital information system ICH Intracranial hemorrhage L Litre MR Mortality rate NPV Negative predictive value TBI Traumatic brain injury μg Microgram Declarations Ethics approval and consent to participate: Ethical approval for the study was provided by the Ethics Committee of the Medical University of Graz (EK: 30-146). Funding statement: The authors have not received a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors. Competing interest statement: None declared. Data availability statement: The data that support the findings of this study are not openly available due to reasons of sensitivity but are available from the corresponding author upon reasonable request. Consent for publication Not applicable Author Contribution C.C.: Conceptualization; methodology; analysis of data; investigation; data curation; writing—original draft preparation. P.P.: Conceptualization; methodology; analysis of data; investigation; data curation; supervision; writing—review and editing. M.M.: Conceptualization; methodology; analysis of data; investigation; data curation. P.S.: Conceptualization; methodology; analysis of data; investigation; data curation; supervision; writing—review and editing. D.K.: Conceptualization; methodology; analysis of data; investigation; data curation. A.L.: Conceptualization; methodology; supervision; writing—review and editing. P.R.: Conceptualization; methodology; analysis of data; investigation; data curation; supervision; writing—review and editing. References Mauritz W, Brazinova A, Majdan M, Leitgeb J (2014) Epidemiology of traumatic brain injury in Austria. Wien Klin Wochenschr. ;126(1–2):42–52. doi: 10.1007/s00508-013-0456-6. Epub 2013 Nov 19. Erratum in: Wien Klin Wochenschr. 2014;126(9–10):324-5. PMID: 24249325; PMCID: PMC3904034 Thaler HW, Schmidsfeld J, Pusch M, Pienaar S, Wunderer J, Pittermann P, Valenta R, Gleiss A, Fialka C, Mousavi M (2015) Evaluation of S100B in the diagnosis of suspected intracranial hemorrhage after minor head injury in patients who are receiving platelet aggregation inhibitors and in patients 65 years of age and older. J Neurosurg 123(5):1202–1208. 10.3171/2014.12.JNS142276 Epub 2015 Jul 7. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6120248","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":422895151,"identity":"f6a077ed-252c-4800-897d-33b1191952b0","order_by":0,"name":"Clemens Clar","email":"","orcid":"","institution":"Medical University of Graz","correspondingAuthor":false,"prefix":"","firstName":"Clemens","middleName":"","lastName":"Clar","suffix":""},{"id":422895152,"identity":"49b561c1-bb0c-4a70-a9eb-0a288732036c","order_by":1,"name":"Paul Puchwein","email":"data:image/png;base64,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","orcid":"","institution":"Medical University of Graz","correspondingAuthor":true,"prefix":"","firstName":"Paul","middleName":"","lastName":"Puchwein","suffix":""},{"id":422895153,"identity":"816018de-7866-4e06-a991-a41167e22e5d","order_by":2,"name":"Maximilian Moshammer","email":"","orcid":"","institution":"Medical University of Graz","correspondingAuthor":false,"prefix":"","firstName":"Maximilian","middleName":"","lastName":"Moshammer","suffix":""},{"id":422895154,"identity":"26a2d7cc-6479-4e7a-a719-85c08cb98a2e","order_by":3,"name":"Patrick Sadoghi","email":"","orcid":"","institution":"Medical University of Graz","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Sadoghi","suffix":""},{"id":422895155,"identity":"e8730f06-59cb-4332-97dc-bf5eac34efa9","order_by":4,"name":"Diether Kramer","email":"","orcid":"","institution":"Medical University of Graz","correspondingAuthor":false,"prefix":"","firstName":"Diether","middleName":"","lastName":"Kramer","suffix":""},{"id":422895156,"identity":"7d892f45-4a64-4359-a599-4e023e3592f7","order_by":5,"name":"Andreas Leither","email":"","orcid":"","institution":"Medical University of Graz","correspondingAuthor":false,"prefix":"","firstName":"Andreas","middleName":"","lastName":"Leither","suffix":""},{"id":422895157,"identity":"be465fc0-2ebe-4de0-950f-39f6e4892d5e","order_by":6,"name":"Patrick Reinbacher","email":"","orcid":"","institution":"Medical University of Graz","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Reinbacher","suffix":""}],"badges":[],"createdAt":"2025-02-27 10:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6120248/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6120248/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":77681452,"identity":"1f9ed617-a50f-4ce0-a089-9826e4eb1442","added_by":"auto","created_at":"2025-03-04 08:39:13","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":152726,"visible":true,"origin":"","legend":"\u003cp\u003eAbsolute frequency of the 11,504 CT findings categorized in outpatient and inpatient cohorts.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6120248/v1/0ef2d4edf8458f75a0d6ca22.jpeg"},{"id":77681457,"identity":"9157ca00-7f73-4a8e-9404-b83b7ce98aa7","added_by":"auto","created_at":"2025-03-04 08:39:15","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":258319,"visible":true,"origin":"","legend":"\u003cp\u003eAge distribution of the 11504 patients, divided into unremarkable CT, hemorrhage possibly fracture, fractur and not assignable, respectively male and female.\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6120248/v1/e947a4bfa8d0b8e2877d83fc.jpeg"},{"id":77681513,"identity":"310a6797-0dff-4ac4-9008-54817fe1e8a6","added_by":"auto","created_at":"2025-03-04 08:39:19","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":180874,"visible":true,"origin":"","legend":"\u003cp\u003eAge distribution of the 11504 patients, divided into inpatients and outpatients, respectively male and female.\u003c/p\u003e","description":"","filename":"floatimage53.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6120248/v1/680373c698232f620f9baf11.jpeg"},{"id":81951166,"identity":"55aaf80d-f58e-440b-98ee-505913a56633","added_by":"auto","created_at":"2025-05-05 09:16:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1084764,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6120248/v1/d126bf89-811d-4cda-8811-9f601746c2a7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Management of traumatic brain injury in an aging population: Role of S100, CT and anticoagulation in 10.051 patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTraumatic brain injury (TBI) is a brain injury commonly caused by trauma, leading to a wide range of symptoms. In Austria the incidence of TBI is 303/100000 with a case fatality rate (CFR) of 3,6% and a mortality rate (MR) of 11/100000 which mirrors the numbers of other detected European countries\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Furthermore, worldwide over 10\u0026nbsp;million TBIs can be diagnosed annually\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e,\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. There is a big gap between the age of patients and the incidence of TBI, heading from 149/100000 for the age of 40\u0026ndash;44 to 1213/100000 for the age of 85\u0026ndash;89\u003csup\u003e1\u003c/sup\u003e. People of advanced age usually suffer from comorbidities like dementia or coronary heart disease (CHD) and are therefore exposed to an increased risk of falling. In addition, the number of blood-thinned patients increases with age, which also increases the risk of TBI\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Diagnosis of TBI often involves interdisciplinary approach and brain imaging techniques such as CT scanning\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Because many emergency departments perform a CT-Scan as their standard diagnostic tool after head injuries, this leads to long waiting periods, a waste of resources and perhaps an unnecessary high exposure of patients to radiation. The decision to perform a CT scan is influenced by various factors, including the severity of symptoms, timing of the injury and the type of trauma.\u003c/p\u003e \u003cp\u003eThe indication for a brain CT scan is partially dependent on the patients clinical presentation, which can be misjudged due to comorbidities like dementia, for example. This is because the symptoms of TBI and this condition can be quite similar. In order to achieve sufficient differentiation between these pathologies, the establishment of clear guidelines and scoring systems is indispensable. Scores such as the Canadian CT Head Rule or the New Orleans Criteria have been distinguished by their high sensitivity\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Nevertheless, the potential influence of dementia on the results has not been accounted for. Furthermore, diagnostic tools that are not of a radiological nature can be utilized.\u003c/p\u003e \u003cp\u003eAs an alternative to the CT scan, which requires radiation, the S100B level has emerged as a promising biomarker-based approach in recent years for diagnosing TBI\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. S100B is a low affinity calcium-binding protein expressed in glial and Schwann cells and is released during an astroglial injury\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Measuring S100B level in the blood can aid in diagnosing TBI and determining the severity of the injury. Some studies suggested that S100B level may serve as a decision-making tool for the necessity of CT scanning\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. We already see a widespread use of that serum marker in certain clinical situations. Guidelines, such as those of the Scandinavian Neurotrauma Committee are already in use of that blood parameter\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e. A more standardized use of this value could prevent almost every third CT\u003csup\u003e\u003cspan additionalcitationids=\"CR11 CR12\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn the following study, we investigated the evidence between S100B level and the need for CT scans in patients with suspected TBI.\u003c/p\u003e \u003cp\u003eThe aim of this study was to detect whether measuring S100B level can be used as an additional diagnostic criterion for CT indication in TBI patients, and if this can help avoid unnecessary CT scans and lead to a reduction in radiation exposure and to a significant improvement of patient outcome.\u003c/p\u003e \u003cp\u003eThe hypothesis was that the S100B level would exhibit high negative sensitivity, thereby potentially obviating the need for CT scans and the associated radiation exposure in certain patients.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eStudy design:\u003c/p\u003e \u003cp\u003eA retrospective single center study was conducted in order to investigate the association between the negative sensitivity of the S100B value and the radiological detection of TBIs. The investigation period ranged from 04/2016 to 07/2022. There was a total of 11504 cases collected.\u003c/p\u003e \u003cp\u003eParticipants:\u003c/p\u003e \u003cp\u003eAll patients admitted to the emergency department of a level I trauma center with a traumatic brain injury were included. The diagnosis of TBI was determined through the following possible pathways:\u003c/p\u003e \u003cp\u003eA patient without acute life-threatening conditions underwent a blood sample collection after a clinical examination by a physician to measure the S100B value. If the S100B value was positive, an urgent CT scan was performed. However, if the S100B value was negative, a physical examination followed by an CT scan was conducted to exclude relevant pathological conditions. If the patient was on anticoagulation at the time of the accident, a CT scan was always performed immediately due to the increased risk of cerebral haemorrhage.\u003c/p\u003e \u003cp\u003ePatients with instable vital parameters or altered neurological status were diagnosed using an urgent CT scan, followed by the measurement of the S100B value after the radiological examination. Those patients, which underwent a CT examination as the initial procedure analyzed. This data was then used to determine the frequency of ultimately unnecessary radiation dosage.\u003c/p\u003e \u003cp\u003eFurthermore, within the cohort under investigation, the cases were documented to identify the number of patients requiring hospital admission. A patient was included in the 'Anticoagulation' subgroup if such medication had been recorded in the Hospital Information System (HIS) or if a specific anticoagulant could be determined through medical history taking. The following medications were included: Coumarins, Heparin and derivative substances, Synthetic pentasaccharide inhibitors of factor Xa, and direct oral anticoagulants (DOACs), direct factor Xa inhibitors and direct thrombin inhibitors.\u003c/p\u003e \u003cp\u003eIn this collective, the comorbidities of individual patients were assessed to see whether the condition of \u0026ldquo;Dementia\u0026rdquo; is associated with an increased risk of hospitalization. A patient was included in the \u0026ldquo;Dementia\u0026rdquo; subgroup if this condition had been recorded in the HIS in the past or had been diagnosed by a specialist.\u003c/p\u003e \u003cp\u003eSince this study is randomized and does not allow any follow-up of patient data, a declaration of consent for participation was not necessary, ethical approval was obtained.\u003c/p\u003e \u003cp\u003eIntervention:\u003c/p\u003e \u003cp\u003eThe S100B value was determined by taking bloodsample through an EDTA tube. This blood sample was then sent to the laboratory at the hospital and analyzed by machine. It is important to mention, that blood samples were only allowed for analysis when taken within the time frame of 30 minutes to 6 hours post-trauma. The threshold for a positive S100B value was set at 0.105 \u0026micro;g /L. Overall, this value was determined upon arrival in the emergency.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eThe patient data was extracted from the HIS. All data were scanned by two independent individuals to minimize errors. These included structured data, like age, gender, coded diagnosis, etc., as well as the clinical reports of the CT scans. The radiological findings were prepared by experienced specialists in radiology and double-checked multiple times. Based on this data cohorts were formed according to age, gender, comorbidities, outpatient/inpatient treatment, diagnosis, and CT findings. For the CT findings, a coding system using 0, 1, and 2 was implemented, where 0 represented a CT scan without acute pathologies, 1 included all recent ICH with or without recent neurocranial fracture, and 2 denoted recent neurocranial fracture without ICH. Post hoc power analysis according to Hoenig and Heisey was calculated according to the magnitude of differences of our main endpoints and revealed that the included number of cases (11,504) was sufficient to reveal a power greater than 80% with a p-value less than 0,05.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIf a CT finding exhibited motion artifacts that prevented sufficient interpretation or if the coding was erroneous, it did not meet the requirements for inclusion and was therefor excluded from this study.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOut of the 11,504 cases included in this study, 3,157 (27%) were initially classified as inpatients and 8,338 (73%) as outpatients. Subsequently, their CTs were categorized as follows: Among the inpatients, 1,833 (58%) exhibited normal CT scans, 605 (19%) showed signs of ICH and/or recent skull fracture, and 301 (10%) displayed recent skull fractures without concurrent ICH (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Additionally, 418 (13%) cases did not meet the requirements and were excluded. Among the outpatients, 7,586 cases (91%) presented normal CT findings, 59 (1%) displayed signs of ICH and/or skull fracture, 265 (3%) showed recent skull fractures without signs of ICH, and 437 (5%) cases were excluded.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eUpon analyzing the entire patient cohort collectively, pathological findings were discovered in 1,230 (11%) out of 11,504 CT scans. Among these, 1230 (11%) CT scans 664 cases (6%) showed evidence of ICH and possible skull fracture and 566 (5%) exhibited skull fractures without concurrent ICH. A total of 9,419 (82%) CT scans were unremarkable, and 855 (7%) had to be excluded.\u003c/p\u003e \u003cp\u003eConsequently, a gender-specific analysis was carried out. Among the inpatients, there was a ratio of 1,850 males (59%) to 1,307 females (41%), whereas among the outpatients, there were 4,533 females (54%) and 3,814 males (46%).\u003c/p\u003e \u003cp\u003eIn the age comparison between inpatient and outpatient treatment, a median age of 64 years was observed for inpatients compared to 74 years for outpatients, with mean ages of 60.7 and 65.6 years, respectively (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eSubsequently, all patients were scanned for surgical interventions documented in the hospital IT system. Among the 8,338 patients treated on an outpatient basis, 28 individuals (0.03%) had recorded surgical procedures. Among the 3,157 inpatients 116 (4%) had documented surgical interventions.\u003c/p\u003e \u003cp\u003eA subgroup analysis was performed on 1,445 patients with pre-existing dementia. While 1,180 (82%) exhibited normal CT scans, 111 (7%) pathological findings were identified with 63 cases (4%) showing signs of ICH with or without possible skull fracture and 48 (3%) exhibiting skull fractures without concurrent ICH. 154 (11%) CT scans were excluded from analysis.\u003c/p\u003e \u003cp\u003eThe patient cohort of 3,920 individuals under known anticoagulation medication revealed that 3,211 (82%) CT scans were unremarkable, 200 (5%) displayed signs of ICH and possible skull fracture, 153 (4%) exhibited skull fractures without concurrent ICH, and 356 (9%) scans were deemed inconclusive.\u003c/p\u003e \u003cp\u003eOut of the total 11,504 cases available, 483 cases with valid S100B measurements were identified, comprising 232 (48%) males and 251 (52%) females. Among this subgroup, 172 (36%) were treated as inpatients, while 311 (64%) received outpatient care. In the age comparison between inpatient and outpatient treatment, a median age of 52 and 32 years, respectively, was determined, with mean ages of 52 and 39 years. The patient cohort undergoing outpatient treatment demonstrated, in 98% of cases with a normal S100B value, concurrent CT scans revealing no recent pathology, thereby indicating an 75% sensitivity of the S100B value. The inpatient cohort exhibited a sensitivity of 80%, and in 73% of cases with a normal S100B value, recent bleedings could not be detected in the CT scans.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe aim of this study was to detect whether measuring S100B level can be used as an additional diagnostic criterion for CT indication in TBI patients, and if this can help avoid unnecessary CT scans and lead to a reduction in radiation exposure and to a significant improvement of patient outcome.\u003c/p\u003e \u003cp\u003eThe hypothesis was that the S100B level would exhibit high negative sensitivity, thereby potentially obviating the need for CT scans and the associated radiation exposure in certain patients. The following study revealed a clear and significant correlation between a negative S100B level and a normal CT scan, with the NPV being 98% for outpatients and 80% for inpatients.\u003c/p\u003e \u003cp\u003eThe initial treatment of TBIs is a highly discussed topic worldwide. In addition to the CT scan, the gold standard diagnostic tool, there has been a significant increase in the number of publications on non-ionizing diagnostic tools for TBI such as the biomarker S100B, which was investigated in this study. Scandinavia even reconsidered the international guidelines and decided to include the S100B value\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. According to these guidelines, the determination of the S100B value is indicated if there is no other risk factor for cerebral pathology present besides unconsciousness and/or vomiting. Therefore, patients on anticoagulation and/or older than 65 years are excluded, which means that this patient group is more frequently exposed to radiation\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. This study clearly confirmed this hypothesis, as risk patients such as patients on anticoagulation had a higher risk of unnecessary CT admission without recent pathology.\u003c/p\u003e \u003cp\u003eConsidering, that an exposure of radiation increases the lifetime risk of developing a malignancy by far, it is essential to evaluate every possibility to avoid unnecessary radiation\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. To assess the increased risk of cancer, the dose used in CT and frequency of performed scans plays an essential role, as higher dosage and large numbers of CTs are associated with an elevated risk of cancer\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. The average dose for an acute brain CT scan is approximately 1\u0026ndash;3 mSv at the detected Level I Trauma center. The following study has demonstrated that around 82% of all CT examinations conducted for TBI did not reveal any pathological findings related to traumatic injuries. Consequently, these patients were exposed to unnecessary radiation. To minimize the risk of unnecessary radiation exposure in the future, the evaluation of new scores and guidelines for CT imaging is strongly indicated\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. Beside radiation issues, economic aspects and 24h availability of CTs and evaluating radiologists could be limiting factors in overloaded health systems worldwide.\u003c/p\u003e \u003cp\u003eFurthermore, we explored the comorbidity of \"dementia\" as a risk factor for hospital admission following TBI. As we demonstrated that only 7% of CT scans in this cohort revealed recent pathology, compared to 11% in the general cohort, the hypothesis that patients with dementia are at an increased risk of unnecessary radiation exposure after TBI was unequivocally confirmed. Clinical diagnosis may be complicated by the overlap of symptoms between dementia and TBI, potentially leading to a more frequent resort to diagnostic measures than necessary. Cognitive limitations typical for dementia and issues in verbal communication can exaggerate the perceived severity of the accident, providing a plausible explanation for the outcomes observed in the subsequent study\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Therefore, a new or adapted screening algorithm, including the development of certain scores and specific guidelines would be warranted to impede the overuse of CT scans in that patient group.\u003c/p\u003e \u003cp\u003eIt was also evident that the cohort of patients under anticoagulation treatment exhibited fewer percentage of detected pathologies overall compared to the entire patient collective. This suggests, among other factors, that the increased risk of bleeding due to anticoagulation lead to a more frequent reliance on CT scans as the primary diagnostic tool. In cases like these, in order to opt for a lower-radiation diagnostic approach, it is clearly indicated to either develop new scoring systems that prominently incorporate the aforementioned factors or to adapt existing ones, such as the \"New Orleans criteria\" or \"Canadian CT head rule,\" to mitigate biases arising from the mentioned pathologies\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eWhen comparing inpatient and outpatient populations, it becomes evident that both the median and average age of the inpatients were significantly higher, indicating an increased likelihood of hospitalization for older individuals after TBI. This result highlights a pronounced disparity in the treatment of traumatic brain injuries based on age, with older patients being subjected to more extended and intensive therapy. Given that more than half of the hospitalized patients exhibited no recent pathology in CT scans, this further underscores the importance of optimizing clear healthcare strategies and establishing well-defined standards.\u003c/p\u003e \u003cp\u003eConsidering that a CT scan costs an average of 250 Euros at the detected hospital, it becomes evident that from an economic perspective, every unnecessary CT scan should be avoided to prevent financial burden on the healthcare system. Additionally, performing a CT scan requires at least one radiologist and a radiological assistant, further adding to the financial implications. This aspect is further emphasized when examining the costs associated with hospitalization, where daily costs of approximately 1293 Euros are incurred per day at the hospital. Thus, implementing new scores and guidelines, as previously discussed, could also benefit the healthcare system by reducing financial burdens.\u003c/p\u003e\n\u003ch3\u003eLimitations:\u003c/h3\u003e\n\u003cp\u003eWe opted to consider the S100B value as negative if it falls below \u0026lt;\u0026thinsp;0.105 \u0026micro;g/L, as this reference value is commonly cited in the literature\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. However, the possibility of a number of subclinical, undetected brain injuries or long-term damages cannot be definitively excluded, as no follow-up was conducted. This study did not differentiate based on ethnic background, which, according to Abdesselam et al.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e, is also an influential factor. Nonetheless, the majority of the patients included were Caucasian, reflecting the demographic composition of Austria.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe following study revealed a clear and significant correlation between a negative S100B level and normal CT scan. We believe that the determination of S100B levels can significantly reduce the radiation exposure for TBI patients. Clear communication of therapeutic aims (e.g. do not escalate, comfort terminal care) in patients with dementia could also help to avoid unnecessary imaging and admission of patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCFR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCase fatality rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCHD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCoronary heart disease\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eComputed tomography\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eDOACs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eDirect oral anticoagulants\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eHIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eHospital information system\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eICH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eIntracranial hemorrhage\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eLitre\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eMR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eMortality rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eNPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eNegative predictive value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eTBI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eTraumatic brain injury\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u0026mu;g\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eMicrogram\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for the study was provided by the Ethics Committee of the Medical University of Graz (EK: 30-146).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding statement: \u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have not received a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone declared.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are not openly available due to reasons of sensitivity but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eC.C.: Conceptualization; methodology; analysis of data; investigation; data curation; writing\u0026mdash;original draft preparation. P.P.: Conceptualization; methodology; analysis of data; investigation; data curation; supervision; writing\u0026mdash;review and editing. M.M.: Conceptualization; methodology; analysis of data; investigation; data curation. P.S.: Conceptualization; methodology; analysis of data; investigation; data curation; supervision; writing\u0026mdash;review and editing. D.K.: Conceptualization; methodology; analysis of data; investigation; data curation. A.L.: Conceptualization; methodology; supervision; writing\u0026mdash;review and editing. P.R.: Conceptualization; methodology; analysis of data; investigation; data curation; supervision; writing\u0026mdash;review and editing.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eMauritz W, Brazinova A, Majdan M, Leitgeb J (2014) Epidemiology of traumatic brain injury in Austria. Wien Klin Wochenschr. ;126(1\u0026ndash;2):42\u0026ndash;52. doi: 10.1007/s00508-013-0456-6. Epub 2013 Nov 19. 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Clin Chem. ;49(5):836-7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1373/49.5.836\u003c/span\u003e\u003cspan address=\"10.1373/49.5.836\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 12709387\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Traumatic brain injury, S100B level, Biomarkers","lastPublishedDoi":"10.21203/rs.3.rs-6120248/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6120248/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eThe aim of this study was to investigate the benefit of the S100B level as a substitute for computed tomography (CT) in assessing brain injury in cases of traumatic brain injury (TBI). The hypothesis was that the S100B level would exhibit high negative sensitivity, thereby potentially obviating the need for CT scans and the associated radiation exposure in certain patients.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eA cohort of 11,504 patient cases with TBI was collected from 04/2016 to 07/2022 at a level I trauma centre, where both CT scans and S100B measurements were performed. Those cases were classified and coded based on diagnosis, age and pathology. These results were analyzed with respect to radiologically diagnosed pathologies and the levels of S100B. Subsequently, a comparison was made to assess the correlation between pathology findings and negative S100B levels.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOut of the 11,504 cases included in this study, 6% showed evidence of intracranial hemorrhage (ICH) and possible neurocranial fracture while 5% exhibited neurocranial fractures without concurrent ICH. The patient cohort of 3,920 individuals under known anticoagulation medication revealed that 5% displayed signs of ICH and possible neurocranial fracture and 4% exhibited neurocranial fractures without concurrent ICH. 483 cases with valid S100B measurements were identified of those, 36% were treated as inpatients showing an NPV of 73%, while 64% received outpatient care showing an NPV of 98%.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eWe found a clear and significant correlation between a negative S100B level and normal CT scan. We believe that the determination of S100B levels significantly reduces the radiation exposure for TBI patients.\u003c/p\u003e","manuscriptTitle":"Management of traumatic brain injury in an aging population: Role of S100, CT and anticoagulation in 10.051 patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-04 08:38:43","doi":"10.21203/rs.3.rs-6120248/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"eb12256e-f99f-4641-8513-0654d994a150","owner":[],"postedDate":"March 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-05T09:08:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-04 08:38:43","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6120248","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6120248","identity":"rs-6120248","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}